SRC mutation enhances colon cancer growth

Gastroenterology News John H. Walsh, Section Editor

SRC Mutation Enhances Colon Cancer Growth

tyrosine can still be phosphorylated, but can no longer bind to the SH2 domain, and thus cannot confer the inactive state. Transfection of this ellular Src (c-Src) is a nonreceptruncated tumor c-Src into cell lines tor tyrosine kinase implicated in leads to transformation, tumor formadevelopment and progression of nution, and promotes merous human canmetastasis. Dr. Encers, including corique Rozengurt of lon cancer. Irby et the UCLA School of al. from the UniverMedicine comments: sity of South Florida ‘‘The key role Src reported in Nature plays in signal transGenetics (February duction is well un1999) that a mutaderstood, but actition in c-Src is found vating mutations of in approximately this enzyme were 12% of patients with not known in huadvanced metastatic man cancers. The colon cancer. This results of this remutation appears to port indicate that prevent c-Src from activating Src mutaforming its retions may play a role pressed state (see Cellular Src is normally maintained in (A) a repressed state by interaction of phosphotyFigure). This inac- rosine in position 530 with an SH-2 domain on the molecule, rendering the catalytic in the malignant tive conformation is domain inactive. This phosphorylation is regulated by the intracellular kinase Csk. (B) progression of hustabilized by both an Active state indicates that dephosphorylation of tyrosine 530 enables the c-Src to man colon cancer undergo a conformational change leading to autophosphorylation of tyrosine in position interaction of a phos- 419 and activation of the catalytic domain. (C) The importance of the C-terminal region and may tell us photyrosine residue that is truncated in the colon cancer mutation immediately after position 530. The more about the moin the carboxyl termi- tyrosine residue at this position is able to be phosphorylated, but can no longer stabilize lecular regulation of the repressed state. Src activity.’’ nus (Y530) with the

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Researchers Fret as NIH Budget Is Squeezed s the party over for biomedical research? The optimism that reigned just a year ago, when National Institutes of Health (NIH) funding was increased by $2 billion amid predictions that its budget would double by 2003, has soured significantly. The President’s proposed FY 2000 NIH budget called for an additional $320 million over FY 1999. To

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New FDA Rules a Boon to Pediatric Research—and Some Drug Companies ew federal regulations designed to provide better information

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SH-2 domain and by further intramolecular contacts mediated by the SH3 domain. The tumor mutation consists of a deletion in the C-terminal tail immediately after the tyrosine residue. The

put that into context, the 2.1% increase would not be enough to keep up with biomedical inflation. In addition, the number of new and competing grants awarded to independent biomedical researchers would be trimmed from 9171 to 7617. Congress was expected to sweeten the pot, but last year’s rosy scenarios seem a distant memory. What happened? Biomedical research supporters lament that spend-

ing on discretionary programs such as the NIH has in recent years been capped by Congress as part of its budget-balancing efforts. The cap was circumvented in the FY 1999 budget via ‘‘emergency spending’’ gimmicks. But these creative accounting maneuvers essentially meant borrowing from the FY 2000 budget, and paying off that debt decreased available discretionary spending even before this year’s process got started.

on pediatric use of new drugs and biologics is likely to be a boon for pediatric clinical investigators, and it may also produce a windfall for the world’s biggest-selling drug. The Food and Drug Administration

Modernization Act of 1997 requires new drugs and biologics that are therapeutically important or commonly used in children to include labeling information on safe pediatric use. The rule also allows the FDA GASTROENTEROLOGY 1999;116:1025–1026